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Cleavage Of CPP32 By Granzyme B Represents A Critical Role For Granzyme B In The Induction Of Target Cell DNA Fragmentation*

A. Darmon, T. Ley, D. Nicholson, R. C. Bleackley
Published 1996 · Biology, Medicine

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Cytotoxic T lymphocytes (CTLs) are able to recognize and destroy target cells bearing foreign antigen using one of two distinct mechanisms: granule- or Fas-mediated cytotoxicity. The exact mechanisms involved in the induction of apoptotic cell death remain elusive; however, it seems likely that a family of cysteine proteases related to interleukin-1β converting enzyme are involved. One family member, CPP32, has been identified as an intracellular substrate for granzyme B, a CTL-specific serine protease responsible for the early induction of target cell DNA fragmentation. Here we use cytolytic cells from granzyme B-deficient mice to confirm that cleavage and activation of CPP32 represents a nonredundant role for granzyme B and that this activation plays a role in the induction of DNA fragmentation in target cells, a signature event for apoptotic cell death. A peptide inhibitor of CPP32-like proteases confirmed the function of these enzymes in fragmentation. 51Cr release was not suppressed under these conditions, suggesting that granzyme B cleavage of CPP32 is primarily involved in the induction of DNA fragmentation and not membrane damage during CTL-induced apoptosis.
This paper references
10.1021/BI00222A027
Human and murine cytotoxic T lymphocyte serine proteases: subsite mapping with peptide thioester substrates and inhibition of enzyme activity and cytolysis by isocoumarins.
S. Odake (1991)
A serine protease (CCP1) is sequestered in the cytoplasmic granules of cytotoxic T lymphocytes.
M. Redmond (1987)
10.1074/JBC.270.26.15870
Molecular Cloning and Pro-apoptotic Activity of ICErelII and ICErelIII, Members of the ICE/CED-3 Family of Cysteine Proteases (*)
N. A. Munday (1995)
10.1615/CRITREVIMMUNOL.V15.I3-4.90
Mechanisms of lysis by cytotoxic T cells.
E. A. Atkinson (1995)
10.1038/376037A0
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
D. Nicholson (1995)
10.1007/978-3-642-79414-8_1
Perforin and granzymes: crucial effector molecules in cytolytic T lymphocyte and natural killer cell-mediated cytotoxicity.
B. Lowin (1995)
10.1038/356768A0
A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes
Nancy A. Thornberry (1992)
10.1016/0092-8674(95)90422-0
Protease activation during apoptosis: Death by a thousand cuts?
S. Martin (1995)
10.1002/PROT.340040306
Comparative molecular model building of two serine proteinases from cytotoxic T lymphocytes
M. E. Murphy (1988)
10.1038/380723A0
Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis
M. Enari (1996)
10.1038/377446A0
Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B
A. Darmon (1995)
10.1074/JBC.270.25.15250
Identification and Characterization of ICH-2, a Novel Member of the Interleukin-1β-converting Enzyme Family of Cysteine Proteases (*)
J. Kamens (1995)
10.1016/0092-8674(94)90376-X
Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells
J. W. Heusel (1994)
10.1016/0092-8674(94)90350-6
An evolutionary perspective on apoptosis
D. Vaux (1994)
10.1016/0092-8674(93)90485-9
The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme
J. Yuan (1993)
10.1074/JBC.271.4.1825
Identification and Characterization of CPP32/Mch2 Homolog 1, a Novel Cysteine Protease Similar to CPP32 (*)
J. Lippke (1996)
Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family.
T. Fernandes-Alnemri (1995)
10.1084/JEM.175.2.553
A natural killer cell granule protein that induces DNA fragmentation and apoptosis
L. Shi (1992)
10.1016/0092-8674(95)90365-8
The CTL's kiss of death
G. Berke (1995)
10.1016/S0092-8674(94)90422-7
Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death
Lin Wang (1994)
10.1073/PNAS.83.5.1448
Cloning of two genes that are specifically expressed in activated cytotoxic T lymphocytes.
C. Lobe (1986)
10.1084/JEM.176.6.1521
Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions
L. Shi (1992)
10.1101/GAD.8.14.1613
Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme.
S. Kumar (1994)
10.1016/0092-8674(87)90544-7
A family of serine esterases in lytic granules of cytolytic T lymphocytes
D. Masson (1987)
10.1016/0092-8674(95)90541-3
Yama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase
M. Tewari (1995)
10.1084/JEM.177.1.195
Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity
E. Rouvier (1993)
10.1016/0092-8674(93)90486-A
Induction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3
M. Miura (1993)
10.1074/JBC.271.18.10816
Processing and Activation of CMH-1 by Granzyme B (*)
Y. Gu (1996)
10.1016/s0021-9258(18)42734-2
Quantitative polymerase chain reaction analysis of cytotoxic cell proteinase gene transcripts in T cells. Pattern of expression is dependent on the nature of the stimulus.
J. Prendergast (1992)
Characterization of a granule-independent lytic mechanism used by CTL hybridomas.
R. Garner (1994)
10.1016/0092-8674(95)90490-5
Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock
P. Li (1995)
10.1007/978-3-642-77014-2_11
Perforin: structure, function, and regulation.
E. Podack (1992)
10.1002/j.1460-2075.1995.tb07183.x
A novel human protease similar to the interleukin‐1 beta converting enzyme induces apoptosis in transfected cells.
C. Faucheu (1995)
10.1016/s0021-9258(18)47344-9
CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme.
T. Fernandes-Alnemri (1994)
10.1126/SCIENCE.3518058
Novel serine proteases encoded by two cytotoxic T lymphocyte-specific genes.
C. Lobe (1986)
Mch3, a novel human apoptotic cysteine protease highly related to CPP32.
T. Fernandes-Alnemri (1995)
10.1084/JEM.183.5.1957
Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death
L. Casciola-Rosen (1996)
10.1073/PNAS.92.12.5679
Natural killer and lymphokine-activated killer cells require granzyme B for the rapid induction of apoptosis in susceptible target cells.
S. Shresta (1995)
10.1126/SCIENCE.1373520
Molecular cloning of the interleukin-1 beta converting enzyme.
D. Cerretti (1992)
10.1002/jlb.58.6.717
Macrophage apoptosis in the absence of active interleukin‐1β‐converting enzyme
M. Nett-Fiordalisi (1995)
10.1074/jbc.271.3.1621
ICE-LAP3, a Novel Mammalian Homologue of the Caenorhabditis elegans Cell Death Protein Ced-3 Is Activated during Fas- and Tumor Necrosis Factor-induced Apoptosis (*)
H. Duan (1996)
10.1016/s0021-9258(18)31596-5
The cytotoxic T cell proteinase granzyme B does not activate interleukin-1 beta-converting enzyme.
A. Darmon (1994)



This paper is referenced by
Implication des lymphocytes B et de BAFF dans l'apoptose des cellules épithéliales des glandes salivaires au cours du syndrome de Gougerot-Sjögren
Marie-Michèle Varin (2012)
10.4049/jimmunol.174.6.3212
Impaired Cytolytic Activity in Calreticulin-Deficient CTLs1
S. Sipione (2005)
Granzimlerin Apoptotik ve Non-Apoptotik Etkileri
E. Keskin (2018)
10.1111/odi.12522
Granzyme B-truncated VEGF fusion protein represses angiogenesis and tumor growth of OSCC.
X-Z Lv (2016)
10.1034/j.1600-065X.2003.00044.x
Granzyme B: a natural born killer
S. Lord (2003)
10.1073/PNAS.0402353101
A proteomic approach for the discovery of protease substrates.
A. Bredemeyer (2004)
10.1073/PNAS.95.6.2956
Bcl-2 expression causes redistribution of glutathione to the nucleus.
D. Voehringer (1998)
10.1139/BCB-75-4-301
The Bcl-xL and Bax-alpha control points: modulation of apoptosis induced by cancer chemotherapy and relation to TPCK-sensitive protease and caspase activation.
E. Schmitt (1997)
10.1093/INTIMM/10.6.719
Apoptosis induced by NK cells is modulated by the NK-active cytokines IL-2 and IL-12.
L. Rodella (1998)
10.1016/S1074-7613(03)00032-3
Granzyme B-induced apoptosis requires both direct caspase activation and relief of caspase inhibition.
I. Goping (2003)
10.1002/1521-4141(200207)32:7<1980::AID-IMMU1980>3.0.CO;2-Z
The differential contribution of granzyme A and granzyme B in cytotoxic T lymphocyte‐mediated apoptosis is determined by the quality of target cells
J. Pardo (2002)
10.1074/jbc.273.22.13703
Transient Poly(ADP-ribosyl)ation of Nuclear Proteins and Role of Poly(ADP-ribose) Polymerase in the Early Stages of Apoptosis*
C. Simbulan-Rosenthal (1998)
10.1016/S0091-679X(01)66017-5
Chapter 16 The (Holey) study of mitochondria in apoptosis
N. Waterhouse (2001)
10.1002/(SICI)1097-0134(19990601)35:4<415::AID-PROT5>3.0.CO;2-7
Electrostatic reversal of serine proteinase substrate specificity
A. Caputo (1999)
Understanding the role of caspase-3 in vivo
M. Woo (2001)
10.1097/00006676-200408000-00004
Caspase-3 Inhibitor Prevents Apoptosis of Human Islets Immediately After Isolation and Improves Islet Graft Function
M. Nakano (2004)
10.1074/jbc.M009038200
Granzyme B-mediated Apoptosis Proceeds Predominantly through a Bcl-2-inhibitable Mitochondrial Pathway* 210
M. Pinkoski (2001)
10.1097/00054725-200008000-00006
Apoptosis: Implications for inflammatory bowel disease
A. Levine (2000)
10.1042/BJ20050687
Cell binding, internalization and cytotoxic activity of human granzyme B expressed in the yeast Pichia pastoris.
U. Giesübel (2006)
Induction of apoptosis in proliferating human endothelial cells by the tumor-specific antiangiogenesis agent combretastatin A-4.
S. Iyer (1998)
10.1016/S0167-4838(99)00282-4
Granzymes (lymphocyte serine proteases): characterization with natural and synthetic substrates and inhibitors.
C. Kam (2000)
10.1016/S0024-3205(99)00538-X
Cytoskeletal disruption induces T cell apoptosis by a caspase-3 mediated mechanism.
H. Suria (1999)
10.1039/A909080K
Enzymatic control of apoptosis.
R. C. Bleackley (2001)
10.2174/138161209788923958
Development of novel, highly cytotoxic fusion constructs containing granzyme B: unique mechanisms and functions.
M. Rosenblum (2009)
10.1016/S0041-1345(98)00652-6
Caspase requirement for the apoptotic death of WR19L-induced by FTY720.
T. Matsuda (1998)
10.1016/S0167-4889(97)00138-9
L is for lytic granules: lysosomes that kill.
L. J. Page (1998)
10.1046/j.1440-1711.1999.00787.x
Regulation of pro‐apoptotic leucocyte granule serine proteinases by intracellular serpins
P. Bird (1999)
10.1016/S0167-4889(99)00131-7
Possible involvement of cytochrome c release and sequential activation of caspases in ceramide-induced apoptosis in SK-N-MC cells.
A. Ito (1999)
GlaxoSmithKline Award Lecture
S. Logue (2008)
MT-21 is a synthetic apoptosis inducer that directly induces cytochrome c release from mitochondria.
M. Watabe (2000)
10.1038/sj.leu.2403240
Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas
J. Muris (2004)
10.1089/VIM.2006.19.391
Herpes simplex virus genes Us3, Us5, and Us12 differentially regulate cytotoxic T lymphocyte-induced cytotoxicity.
M. Aubert (2006)
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